Epithelial cells of the alveolus form the interface between the environment and the circulation and, in doing so, provide a surface through which gas exchange occurs rapidly and efficiently in normal individuals. This barrier is compromised, that is, thickened or destroyed, in many lung diseases, but alveolar repair reestablishes type I and II cells with normal structure and normal differentiated function. Because of the importance of the peripheral lung in gas exchange, we have chosen to study epithelial cells which comprise the alveolar wall. We will first devise methods for the isolation of human type II cells, and later type I cells, from surgical specimens. Using a satisfactory type II cell preparation, we will characterize the cells and their secretion by biochemical and morphologic methods. We will determine phospholipid composition as indicative of pulmonary surfactant, and we will ident fy agents which stimulate surfactant secretion. Clinically relevant drugs will be tested to determine whether they increase, decrease, or have no effect on secretion. The protein composition of the cells and secretions will be studied in detail because of the importance of proteins on surfactant function and because they confer specificity to cell types and cell surfaces. Methods will be sought which support differentiated type II cell functions in vitro to provide a system for the study of factors which influence type II cell proliferation. We will seek methods for the isolation and purification of type I cells. The lipid and protein composition of the cells will be analyzed chemically and, if the cells are viable, they will be placed in culture and used to characterize cellular responses to injurious agents. Type I cells will also be used to develop type I cell-specific markers. When available, these will permit us to characterize type II-type I cell transformation in vitro.